The use of drugs for therapeutic purposes would be greatly enhanced by a method which would introduce them selectively into those cells where the pharmacological action is needed. Several approaches to accomplish this purpose have been investigated. Two groups of investigators; J. C. Chabala and T. Y. Shen, Carbohyd. Res., 67, 55 (1978); M. M. Ponpipom, R. L. Bugianesi, and T. Y. Shen, Canad. J. Chem. 58, 214 (1980), M. R. Mauk, R. C. Gamble and J. D. Baldeschwieler, Science 207, 309 (1980); Proc. Natl. Acad. Sci. U.S.A. 77, 4430 (1980), have synthesized and incorporated glycolipids into liposomes and studied their distribution in vivo showing the importance of carbohydrates as cell-surface determinants.
Other investigators have studied the use of human albumin microspheres covalently coupled to succinoyl-Ala-Ala-Pro-ValCH.sub.2 Cl which is an active site-directed inhibitor of human leukocyte elastase. These investigators reported that such conjugates directed the inhibitor to the lungs when administered intravenously in rats, R. R. Martodam, D. Y. Twumasi, I. E. Liener, J. C. Powers, N. Nishino and G. Krejcarek, Proc. Natl. Acad. Sci. U.S.A. 76, 2128 (1979). Earlier work of G. Ashwell and A. Morell, Adv. Enzmol. 41, 99 (1974) demonstrated that exposed sugar residues in glycoproteins serve as determinants for in vivo (i.e. clearance) and in vitro (i.e. uptake) recognition.
Many other selective drug delivery systems have been described, G. Gregoriadis (Ed.) "Drug Carriers in Biology and Medicine", Academic Press 1979; Nature 265, 407 (1977) including binding a drug or dose of radioactive atom to tumor specific antibodies. In addition, deoxynucleic acid (DNA) has been used as a carrier for antitumor drugs such as daunorubicin, adriamycin and ethidium bromide.
These methods, although useful in certain cases have some problems. In some cases the targeting is too imprecise and the payload too small. Use of DNA and liposomes as carriers also has certain problems related to potential toxicity and pharmaceutical requirements.
The present invention provides a tissue specific ligand which is chemically bound to a bioactive agent for administration and which is specific in its targeting ability. The ligand is carefully selected to avoid toxicity or side effects and is relatively easy to prepare and standardize for in vivo administration.